Intracoronary 17beta-estradiol and the inotropic response to dobutamine in postmenopausal women.
BACKGROUND
Gender differences with respect to clinical presentation and outcome of cardiovascular disease have prompted examination of sex-specific factors that may influence cardiovascular physiology and pathophysiology. The rationale for evaluating control of contractility by estrogen derives from preclinical data demonstrating that 17beta-estradiol (17beta-E(2)) can attenuate the myocardial response to adrenergic stimulation.


METHODS
The effects of two doses of intracoronary 17beta-E(2) (150 and 300 ng/min) were tested on the left ventricular (LV) inotropic response to intravenous dobutamine in postmenopausal women who had undergone diagnostic cardiac catheterization. Peak positive LV+dP/dt (LV+dP/dt(max)) was obtained from analysis of LV pressure recorded by a micromanometer catheter.


RESULTS
The study was terminated prematurely after the manufacturer stopped production of 17beta-E(2), and data from 7 patients who had completed the study were analyzed. Intracoronary 17beta-E(2) had no effect on basal LV+dP/dt(max) (1299 +/- 60 mm Hg/sec [mean +/- SE] at control vs, 1299 +/- 46 mm Hg/sec with 17beta-E(2)). Intracoronary 17beta-E(2) also had no significant effect on the LV+dP/dt(max) response to dobutamine (1672 +/- 95 mm Hg/sec with dobutamine alone vs. 1639 +/- 73 with dobutamine and 17beta-E(2), p = 0.51).


CONCLUSIONS
In humans, no evidence of an acute moderate or large effect of 17beta-E(2) on adrenergically stimulated contractility was documented; a small effect size could not be excluded.
Mak
Susanna
S
Clinical Cardiovascular Research Laboratory, Mount Sinai Hospital, and Division of Cardiology, Department of Medicine, University of Toronto, Ontario, Canada. smak@mtsinai.on.ca
D000704:Analysis of Variance; D006328:Cardiac Catheterization; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D004347:Drug Interactions; D004562:Electrocardiography; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D013739:Testosterone / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D004967:Estrogens; D004280:Dobutamine; D013739:Testosterone; D004958:Estradiol